Apoptosis is necessary for proper embryological development and tissue homeostasis in adults. Consequently, a central feature of cancer progression and degenerative disorders is dysregulation of apoptosis. Our lab recently identified a family of nonstructural small (NSs) proteins from the Bunyavirus family that share homology to the known apoptotic inducer Reaper from Drosophila melanogaster. Furthermore, Bunyaviruses are the leading cause of pediatric encephalitis in North America. The overall goal of this proposal is to characterize the role of Reaper and the NSs proteins during vertebrate apoptosis. A more complete understanding of Reaper/NSs modulated apoptotic signaling will enable the development of more specific, effective therapeutics directed towards cancer, neurodegenerative disease, and Bunyaviral encephalitis. This proposal will use the Xenopus egg extract and cultured human cells to more fully characterize Reaper and NSs protein function; these approaches should yield increased understanding of vertebrate apoptosis while offering insight into the mechanism of Bunyaviral pathogenicity. [unreadable] [unreadable]